title: Predictors of response to tiotropium versus salmeterol in asthmatic adults.
abstract: BACKGROUND
  Tiotropium has activity as an asthma controller. However, predictors of a positive response to tiotropium have not been described.
  
  
  OBJECTIVE
  We sought to describe individual and differential responses of asthmatic patients to salmeterol and tiotropium when added to an inhaled corticosteroid, as well as predictors of a positive clinical response.
  
  
  METHODS
  Data from the double-blind, 3-way, crossover National Heart, Lung, and Blood Institute's Asthma Clinical Research Network's Tiotropium Bromide as an Alternative to Increased Inhaled Glucocorticoid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid (ClinicalTrials.gov number, NCT00565266) trial were analyzed for individual and differential treatment responses to salmeterol and tiotropium and predictors of a positive response to the end points FEV1, morning peak expiratory flow (PEF), and asthma control days (ACDs).
  
  
  RESULTS
  Although approximately equal numbers of patients showed a differential response to salmeterol and tiotropium in terms of morning PEF (n = 90 and 78, respectively) and ACDs (n = 49 and 53, respectively), more showed a differential response to tiotropium for FEV1 (n = 104) than salmeterol (n = 62). An acute response to a short-acting bronchodilator, especially albuterol, predicted a positive clinical response to tiotropium for FEV1 (odds ratio, 4.08; 95% CI, 2.00-8.31; P < .001) and morning PEF (odds ratio, 2.12; 95% CI, 1.12-4.01; P = 0.021), as did a decreased FEV1/forced vital capacity ratio (FEV1 response increased 0.39% of baseline for every 1% decrease in FEV1/forced vital capacity ratio). Higher cholinergic tone was also a predictor, whereas ethnicity, sex, atopy, IgE level, sputum eosinophil count, fraction of exhaled nitric oxide, asthma duration, and body mass index were not.
  
  
  CONCLUSIONS
  Although these results require confirmation, predictors of a positive clinical response to tiotropium include a positive response to albuterol and airway obstruction, factors that could help identify appropriate patients for this therapy.
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, NC. Electronic address: sppeters@wakehealth.edu.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Kunselman
authors.forename: Nikolina
authors.initials: N
authors.lastname: Icitovic
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Moore
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Pascual
authors.forename: Bill T
authors.initials: BT
authors.lastname: Ameredes
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.forename: William J
authors.initials: WJ
authors.lastname: Calhoun
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Reuben M
authors.initials: RM
authors.lastname: Cherniack
authors.forename: Timothy
authors.initials: T
authors.lastname: Craig
authors.forename: Loren C
authors.initials: LC
authors.lastname: Denlinger
authors.forename: Linda L
authors.initials: LL
authors.lastname: Engle
authors.forename: Emily A
authors.initials: EA
authors.lastname: Dimango
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Lazarus
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
authors.forename: Njira
authors.initials: N
authors.lastname: Lugogo
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
authors.forename: Joe
authors.initials: J
authors.lastname: Ramsdell
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
authors.forename: E Rand
authors.initials: ER
authors.lastname: Sutherland
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Wasserman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Walter
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wechsler
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use*; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D000069447:Tiotropium Bromide
keywords: ACD; ACRN; Asthma; Asthma Clinical Research Network; Asthma control day; FVC; Forced vital capacity; HFA; Hydrofluoroalkane; ICS; Inhaled corticosteroid; LABA; LAMA; Long-acting muscarinic antagonist; Long-acting β-agonist; NHLBI; National Heart, Lung, and Blood Institute; OR; Odds ratio; PEF; Peak expiratory flow; TALC; Tiotropium Bromide as an Alternative to Increased Inhaled Glucocorticoid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid (ClinicalTrials.gov number, NCT00565266) trial; predictor of response; responder analysis; salmeterol; tiotropium